2.02012-05-31 13:46:37 -06002015-06-03 15:53:47 -0600ECMDB01163M2MDB000279Guanosine diphosphate mannoseGDP-mannose is a nucleoside diphosphate sugar that is important in the production of fucosylated oligosaccharides. GDP-mannose is transformed to GDP-fucose via three enzymatic reactions carried out by two proteins, GDP-mannose 4,6-dehydratase (GMD) and a second enzyme, GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase. GDP-mannose 4,6-dehydratase (EC 4.2.1.47) catalyzes the chemical reaction: GDP-mannose <--> GDP-4-dehydro-6-deoxy-D-mannose + H2O. The epimerase converts the GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose. (PMID: 12651883). GDP-mannose is also synthesized from mannose 1-phosphate via the enzyme ATP-mannose-1-phosphate-guanyltransferase and GTP. GDP MannoseGDP-D-MannoseGDP-GlucoseGDP-ManGDP-MannoseGDP-α-D-mannoseGuanosine Diphosphate MannoseGuanosine diphosphomannoseGuanosine diphosphoric acid mannoseGuanosine pyrophosphate mannoseGuanosine pyrophosphoric acid mannoseC16H25N5O16P2605.3411605.077152801[({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy})phosphinic acidguanosine diphosphomannose3123-67-9NC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(=O)O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)[C@@H](O)[C@H]2O)C(=O)N1InChI=1S/C16H25N5O16P2/c17-16-19-12-6(13(28)20-16)18-3-21(12)14-10(26)8(24)5(34-14)2-33-38(29,30)37-39(31,32)36-15-11(27)9(25)7(23)4(1-22)35-15/h3-5,7-11,14-15,22-27H,1-2H2,(H,29,30)(H,31,32)(H3,17,19,20,28)/t4-,5-,7-,8-,9+,10-,11+,14-,15-/m1/s1MVMSCBBUIHUTGJ-GDJBGNAASA-NSolidCytosollogp-1.76logs-1.89solubility7.77e+00 g/llogp-5.3pka_strongest_acidic1.73pka_strongest_basic-3.6iupac[({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy})phosphinic acidaverage_mass605.3411mono_mass605.077152801smilesNC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(=O)O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)[C@@H](O)[C@H]2O)C(=O)N1formulaC16H25N5O16P2inchiInChI=1S/C16H25N5O16P2/c17-16-19-12-6(13(28)20-16)18-3-21(12)14-10(26)8(24)5(34-14)2-33-38(29,30)37-39(31,32)36-15-11(27)9(25)7(23)4(1-22)35-15/h3-5,7-11,14-15,22-27H,1-2H2,(H,29,30)(H,31,32)(H3,17,19,20,28)/t4-,5-,7-,8-,9+,10-,11+,14-,15-/m1/s1inchikeyMVMSCBBUIHUTGJ-GDJBGNAASA-Npolar_surface_area327.43refractivity118.51polarizability48.72rotatable_bond_count9acceptor_count16donor_count10physiological_charge-2formal_charge0Fructose and mannose metabolismec00051Ascorbate and aldarate metabolismec00053Amino sugar and nucleotide sugar metabolismec00520Metabolic pathwayseco01100Amino sugar and nucleotide sugar metabolism IIThe synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate.
N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound is then deaminased into Beta-D-fructofuranose 6-phosphate through a glucosamine-6-phosphate deaminase.
The beta-D-fructofuranose 6 -phosphate is isomerized in a reversible reaction into an alpha-D-mannose 6-phosphate. This compound can also be introduced into the cell from the periplasmic space through a mannose PTS permease that phosphorylates an alpha-D-mannose. Alpha-D-mannose 6-phosphate undergoes a reversible reaction through a phosphomannomutase to produce an alpha-D-mannose 1-phosphate.
The alpha-D-mannose 1-phosphate enters the nucleotide sugar metabolism through a reaction with GTP producing a GDP-mannose and releasing a pyrophosphate, all through a mannose-1-phosphate guanylyltransferase. GDP-mannose is then dehydrated to produce GDP-4-dehydro-6-deoxy-alpha-D-mannose through a GDP-mannose 4,6-dehydratase. This compound is then used to synthesize GDP-Beta-L-fucose through a NADPH dependent GDP-L-fucose synthase.
Alpha-D-glucose is introduced into the cytoplasm through a glucose PTS permease, which phosphorylates the compound in order to produce an alpha-D-glucose 6-phosphate. This compound is then modified through a phosphoglucomutase 1 to yield alpha-D-glucose 1-phosphate. This compound can either be adenylated to produce ADP-glucose or uridylylated to produce galactose 1-phosphate through glucose-1-phosphate adenyllyltransferase and galactose-1-phosphate uridylyltransferase respectively.PW000887MetabolicMannose Metabolism
D-mannose can serve as a total source of carbon and energy for growth of E. coli. Alpha-D-mannose is introduced into the cytoplasm through a mannose PTS permease.
Because mannose is taken up via a phosphotransferase system (PTS), the first intracellular species is D-mannose-6-phosphate. mannose-6-phosphate isomerase converts D-mannose-6-phosphate to D-fructose-6-phosphate, an intermediate of glycolysis, and hence it flows through the pathways of central metabolism to satisfy the cell's need for precursor metabolites, reducing power, and metabolic energy.
The first two enzymes in the pathway (SEE VERTICAL SECTION) catalyze isomerizations that interconvert phosphorylated aldohexoses (β-D-glucose-6-phosphate, D-mannose-6-phosphate) and phosphorylated ketohexoses (D-fructose-6-phosphate). The reaction catalyzed by mannose-6-phosphate isomerase that produces D-mannose-6-phosphate is the first committed step in the biosynthesis of the activated mannose donor GDP-α-D-mannose. D-mannose-6-phosphate is then converted to GDP-D-mannose by the interaction of phosphomannomutase and mannose-1-phosphate guanylyltransferase .
As for the bottom part L-fucose is biosynthesized as the sugar nucleotide GDP-L-fucose. Its biosynthesis from GDP-D-mannose begins with dehydration of this compound to GDP-4-dehydro-6-deoxy-D-mannose by the product of gene gmd. Then the bifunctional GDP-fucose synthase catalyzes the two-step (epimerase/reductase) synthesis of GDP-fucose from GDP-4-dehydro-6-deoxy-D-mannose via a GDP-4-dehydro-6-L-deoxygalactose intermediate. L-fucose is then incorporated into the colanic acid building blocks biosynthesis pathway.PW000822Metaboliccolanic acid building blocks biosynthesisThe colonic acid building blocks biosynthesis starts with a Beta-D-Glucose undergoing a transport reaction mediated by a glucose PTS permease. The permease phosphorylates the Beta-D-Glucose, producing a Beta-D-Glucose 6-phosphate. This compound can either change to an Alpha-D-Glucose 6-phosphate spontaneously or into a fructose 6-phosphate through a glucose-6-phosphate isomerase. The latter compound can also be present in E.coli through the interaction of D-fructose and a mannose PTS permease which phosphorylate the D-fructose.
Fructose 6-phosphate interacts in a reversible reaction with mannose-6-phosphate isomerase in order to produce a Alpha-D-mannose 6-phosphate. This compound can also be present in E.coli through the interaction of Alpha-D-mannose and a mannose PTS permease which phosphorylates the alpha-D-mannose. Alpha-D-mannose 6-phosphate interacts in a reversible reaction with a phosphomannomutase to produce a alpha-D-mannose 1-phosphate. This compound in turn with a hydrogen ion and gtp undergoes a reaction with a mannose-1-phosphate guanylyltransferase, releasing a pyrophosphate and producing a guanosine diphosphate mannose. Guanosine diphosphate mannose interacts with gdp-mannose 4,6-dehydratase releasing a water, and gdp-4-dehydro-6-deoxy-D-mannose. This compound in turn with hydrogen ion and NADPH interact with GDP-L-fucose synthase releasing NADP and producing a GDP-L-fucose.
The Alpha-D-Glucose 6-phosphate interacts in a reversible reaction with phosphoglucomutase-1 to produce a alpha-D-glucose 1-phosphate. This in turn with UTP and hydrogen ion interact with UTP--glucose-1-phosphate uridyleltransferase releasing a pyrophosphate and UDP-glucose.
UDP-glucose can either interact with galactose-1-phosphate uridylyltransferase to produce a UDP-galactose or in turn with NAD and water interact with UDP-glucose 6-dehydrogenase releasing a NADH and a hydrogen ion and producing a UDP-glucuronate.
GDP-L-fucose, UDP-glucose, UDP-galactose and UDP-glucuronate are sugars that need to be activated in the form of nucleotide sugar prior to their assembly into colanic acid, also known as M antigen.
Colanic acid is an extracellular polysaccharide which has been linked to a cluster of 19 genes(wca).
PW000951MetabolicGDP-mannose biosynthesisPWY-5659GDP-L-fucose biosynthesis I (from GDP-D-mannose)PWY-66Specdb::CMs9956Specdb::CMs37952Specdb::CMs475905Specdb::CMs475906Specdb::CMs475907Specdb::CMs475908Specdb::CMs475909Specdb::CMs475910Specdb::CMs475911Specdb::CMs475912Specdb::CMs475913Specdb::CMs475914Specdb::CMs475915Specdb::CMs475916Specdb::CMs475917Specdb::CMs475918Specdb::CMs475919Specdb::CMs475920Specdb::CMs475921Specdb::CMs475922Specdb::CMs475923Specdb::CMs475924Specdb::CMs475925Specdb::CMs475926Specdb::CMs475927Specdb::NmrOneD21282Specdb::NmrOneD21283Specdb::NmrOneD21284Specdb::NmrOneD21285Specdb::NmrOneD21286Specdb::NmrOneD21287Specdb::NmrOneD21288Specdb::NmrOneD21289Specdb::NmrOneD21290Specdb::NmrOneD21291Specdb::NmrOneD21292Specdb::NmrOneD21293Specdb::NmrOneD21294Specdb::NmrOneD21295Specdb::NmrOneD21296Specdb::NmrOneD21297Specdb::NmrOneD21298Specdb::NmrOneD21299Specdb::NmrOneD21300Specdb::NmrOneD21301Specdb::MsMs23411Specdb::MsMs23412Specdb::MsMs23413Specdb::MsMs30209Specdb::MsMs30210Specdb::MsMs30211Specdb::MsMs1470784Specdb::MsMs1471120Specdb::MsMs2226603Specdb::MsMs2228143Specdb::MsMs2228918Specdb::MsMs2230503Specdb::MsMs2231263Specdb::MsMs2232960Specdb::MsMs2757834Specdb::MsMs2757835Specdb::MsMs2757836Specdb::MsMs2948451Specdb::MsMs2948452Specdb::MsMs2948453HMDB0116373217372C0009615820GDP-MANNOSEGDDGuanosine diphosphate mannoseKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25.17765195Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Becker, D. J., Lowe, J. B. (2003). "Fucose: biosynthesis and biological function in mammals." Glycobiology 13:41R-53R.12651883Huang, Gang-Liang; Liu, Xiang; Zhang, Hou-Cheng; Wang, Peng-George. A facile two-step chemo-enzymatic synthesis of GDP-mannose. Letters in Organic Chemistry (2006), 3(9), 668-669. GDP-mannose 4,6-dehydrataseP0AC88GM4D_ECOLIgmdhttp://ecmdb.ca/proteins/P0AC88.xmlMannose-1-phosphate guanylyltransferaseP24174MANC_ECOLImanChttp://ecmdb.ca/proteins/P24174.xmlGDP-mannose mannosyl hydrolaseP32056NUDD_ECOLInudDhttp://ecmdb.ca/proteins/P32056.xmlGDP-mannose pyrophosphatase nudKP37128NUDK_ECOLInudKhttp://ecmdb.ca/proteins/P37128.xmlGuanosine diphosphate + Hydrogen ion + D-Mannose 1-phosphate > Guanosine diphosphate mannose + PhosphateGuanosine diphosphate mannose + Water > Guanosine diphosphate + Hydrogen ion + D-MannoseGDPMANMANHYDRO-RXNGuanosine diphosphate mannose <> GDP-4-Dehydro-6-deoxy-D-mannose + WaterR00888GDPMANDEHYDRA-RXNGuanosine diphosphate mannose + Water > Guanosine monophosphate +2 Hydrogen ion + D-Mannose 1-phosphateRXN0-5108Guanosine triphosphate + D-Mannose 1-phosphate <> Pyrophosphate + Guanosine diphosphate mannoseR008852.7.7.13-RXNGuanosine diphosphate mannose + Water > Hydrogen ion + Guanosine monophosphate + D-Mannose 1-phosphateRXN0-5108Hydrogen ion + D-Mannose 1-phosphate + Guanosine triphosphate > Guanosine diphosphate mannose + Pyrophosphate2.7.7.13-RXNGuanosine diphosphate mannose > Water + GDP-4-Dehydro-6-deoxy-D-mannoseGDPMANDEHYDRA-RXNGuanosine diphosphate mannose + Water > Guanosine diphosphate + D-MannoseGuanosine triphosphate + Alpha-D-mannose 1-phosphate > Pyrophosphate + Guanosine diphosphate mannoseGuanosine diphosphate mannose + Water > Guanosine monophosphate + Alpha-D-mannose 1-phosphateD-Mannose 1-phosphate + Guanosine triphosphate + Hydrogen ion > Pyrophosphate + Guanosine diphosphate mannosePW_R002961α-D-mannose 1-phosphate + Guanosine triphosphate + Hydrogen ion > Guanosine diphosphate mannose + PyrophosphatePW_R003361Guanosine diphosphate mannose > Water + GDP-4-dehydro-6-deoxy-α-D-mannosePW_R003362Guanosine diphosphate mannose > GDP-4-Dehydro-6-L-deoxygalactose + GDP-4-Dehydro-6-L-deoxygalactosePW_R005171Guanosine triphosphate + D-Mannose 1-phosphate <> Pyrophosphate + Guanosine diphosphate mannoseGuanosine diphosphate mannose <> GDP-4-Dehydro-6-deoxy-D-mannose + WaterGuanosine triphosphate + D-Mannose 1-phosphate <> Pyrophosphate + Guanosine diphosphate mannoseGuanosine diphosphate mannose <> GDP-4-Dehydro-6-deoxy-D-mannose + Water